RUI: Mechanisms of Transcriptional Repression by Sequence Specific Transcription Factors

RUI：序列特异性转录因子的转录抑制机制

• 批准号: 2016342
• 负责人: Heather Griscom
• 金额: $ 101.72万
• 依托单位: James Madison University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2016342&HistoricalAwards=false
• 关键词: RUI; Mechanisms; Transcriptional; Repression; Sequence

This project uses an integrated sciences approach to further understanding of how the cellular machinery coordinates gene expression as an embryo grows and develops prior to birth and to test computational models of that coordination from birth through adulthood, allowing scientists to correlate the regulation of gene expression with critical developmental events like cellular specification and embryonic morphogenesis. Through a combination of course-based undergraduate research experiences (CUREs) and independent mentored research, undergraduate students will use genetics, molecular biology, mathematical modeling, and artificial neural networks to model protein-DNA interactions that inhibit gene expression, while Masters students will engage in discipline-based education research (DBER) to understand how CUREs promote student outcomes and student retention in STEM. This project also promotes the engagement of students and faculty with scientists from groups that are traditionally underrepresented in STEM, through a seminar/workshop series titled “Representation Matters” that aims to increase the retention of underrepresented scientists in STEM fields.The research objective of this project is to understand the molecular mechanisms by which HES proteins mediate transcriptional repression during embryogenesis and to use that information to test predictions of HES mediated repression genome-wide and across developmental stages, using Caenorhabditis elegans as a model system. Undergraduates students will use ChIP-seq, RNA-seq, RNA-interference, and co-immunoprecipitation to define the cis- and trans-regulatory contexts of HES-mediated repression. Masters students and a postdoctoral fellow will use ChIP-seq and ChiP-PCR to determine if promoter or enhancer occupancy by HES proteins influences RNA polymerase occupancy or chromatin status. These data will be used to build models and to test predictions of HES-mediated repression during embryogenesis using deep learning or neural network semi-supervised models. The broader impacts objective of this project is to provide foundational research experiences for undergraduate and Masters students while enhancing training and mentoring experiences of students from underrepresented groups. A multi-faceted approach that includes mentored research experiences, CUREs that reinforce fundamental principles in biology and that introduce computational modeling, and activities that intentionally promote professional and social interactions between students and scientists of color, will examine perceived and actual outcomes of student learning, self-identification and social awareness.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

该项目采用综合科学方法，进一步了解细胞机制如何协调基因表达，因为胚胎在出生前生长和发育，并测试从出生到成年的协调计算模型，使科学家能够将基因表达的调节与关键发育事件相关联，如细胞规格和胚胎形态发生。通过基于课程的本科研究经验（CURES）和独立的指导研究相结合，本科生将使用遗传学，分子生物学，数学建模和人工神经网络来模拟抑制基因表达的蛋白质-DNA相互作用，而硕士生将从事基于学科的教育研究（DBER），以了解CURES如何促进学生的成绩和学生在STEM中的保留。该项目还促进了学生和教师与来自传统上在STEM中代表性不足的群体的科学家的接触，通过题为“代表问题”的系列研讨会/讲习班，该项目的研究目标是了解HES蛋白在胚胎发生过程中介导转录抑制的分子机制，并利用这些信息以秀丽隐杆线虫为模型系统，测试HES介导的全基因组和跨发育阶段阻遏的预测。本科生将使用ChIP-seq，RNA-seq，RNA干扰和免疫共沉淀来定义HES介导的抑制的顺式和反式调节背景。硕士生和博士后研究员将使用ChIP-seq和ChIP-PCR来确定HES蛋白的启动子或增强子占用率是否影响RNA聚合酶占用率或染色质状态。这些数据将用于构建模型，并使用深度学习或神经网络半监督模型来测试胚胎发生过程中HES介导的抑制的预测。该项目更广泛的影响目标是为本科生和硕士生提供基础研究经验，同时加强代表性不足群体学生的培训和指导经验。一个多方面的方法，包括指导的研究经验，加强生物学的基本原则，并引入计算建模的CURE，以及有意促进学生和有色人种科学家之间的专业和社会互动的活动，将检查学生学习的感知和实际结果，自该奖项反映了NSF的法定使命，并被认为值得通过使用基金会的智力价值和更广泛的评估来支持。影响审查标准。